Formation and evaluation of mechanism-based chemical categories for regulatory read-across assessment of repeated-dose toxicity: A case of hemolytic anemia.

The aim of this study is to define chemical categories that can be applied to regulatory read-across assessments for repeated-dose toxicity, by classifying toxic substances based on their structures and mechanism of actions (MoAs). Hemolytic anemia, which often appears primarily, was examined as an example. An integrated database was constructed by collecting publicly available datasets on repeated-dose toxicity, in which 423 out of a total of 1518 chemicals were identified as capable of inducing hemolytic anemia.

Constructing a developmental and reproductive toxicity database of chemicals (DART NIHS DB) for integrated approaches to testing and assessment.

Developmental and reproductive toxicity (DART) is an important endpoint, and databases (DBs) are essential for evaluating the risk of untested substances using alternative methods. We have constructed a reliable and transparent DART DB, which we named DART NIHS DB, using the publicly available datasets of DART studies of industrial chemicals conducted by Japanese government ministries in accordance with the corresponding OECD test guidelines (OECD TG421 and TG422). This DB is unique because its dataset chemicals have little overlap with those of ToxRefDB, which compiles large-scale DART data, and it is reliable because the included datasets were created after reviewing the individual study reports.

Determination of serum 7-ketocholesterol concentrations and their relationships with coronary multiple risks in diabetes mellitus.

Oxysterols have cytotoxic effects and contribute to the development of atherosclerosis. To examine association between 7-ketocholesterol and diabetes mellitus, and other coronary risk factors, we developed a reliable quantitative method to measure serum 7-ketocholesterol (s-7KCHO) and studied s-7KCHO in patients with type 2 diabetes mellitus (T2DM). The s-7KCHO was detected by gas chromatography-mass spectrometry assay.